Treated bandages or patches have been devised in the past as aids in stopping the flow of blood from wounds, cuts, scratches and the like. Generally, the approach taken has been to formulate a composition which includes a clotting agent with or without a germicidal or antiseptic agent and to saturate the pad or gauze strip on the bandage with that solution. For instance, U.S. Pat. No. to Curtis 2,579,367 discloses the formulation of a bandage in which a proteinaceous aqueous solution or paste is applied to the area to be treated, followed by the application of a protein coagulant which will be converted into an insoluble semipermeable artificial eschar. The suggested composition of the protein coagulant in that patent is from selected metal salts including water soluble salts of divalent zinc, manganese and cobalt and specifically zinc acetate, cobalt sulfur and manganese sulfate. It is proposed that this composition be applied to a surgical gauze and permitted to dry after which the gauze is applied to a coating of the protein paste over a wound so that the paste reacts with the metal salt of the bandage to form a metal caseinate. Others have proposed the use of various types of bandages or pads treated with a clotting agent, such as, for example, U.S. Pat. Nos. to Beardsley 2,442,111; Zaffaroni 3,731,683; Edinbaum 3,342,183; Schattner 3,317,376; and Anderson 3,328,259. In the past, however, none have devised an effective method of preparing a prepackaged coagulation composition which by proper storage can be applied as a dressing to a wound and operate effectively to convert fibrinogen in the blood to a fibrin clot.
The importance of acting directly upon the fibrinogen can be best appreciated by a consideration of the blood coagulation mechanism. Generally speaking, the unaltered clotting factor, known as a proenzyme, is converted to an active enzyme which is capable in turn of converting thousands of substrate molecules into active enzymes. This initiates a chain reaction whereby activation of a single proenzyme molecule may lead to activation of the entire clotting mechanism. On the other hand, the fibrinolytic system in the body is antagonistic to the clotting mechanism and maintains a balance between clot formation and clot lysis. In the fibrinolytic system, a series of proenzymes when activated are converted to enzymes which are capable of dissolving blood clots, the dissolving or lytic enzyme being referred to as plasmin. However, many factors can occur to upset the balance between clot formation and clot lysis. It is not the purpose in discussing the background of this invention to consider those factors which may interrupt the chain reaction or sequence in clotting. It is important to recognize, however, that most desirably the clotting activity should occur at a low point in the sequence or chain reaction and specifically be at the site of the wound so that the coagulation mechanism will not be interrupted by other upsetting factors in the sequence. This approach will minimize the risk of the coagulating agent entering the bloodstream and cause the clotting to occur most rapidly and superficially at the site of the wound.
Thrombin is a sterile protein substance prepared from prothrombin through interaction with added thromboplastin usually in the presence of calcium. In concentrated form, it has a potent clotting effect on the blood and specifically in coagulating plasma fibrinogen converting same to a fibrin clot. Customarily, thrombin is available in powder form mixed with minor proportions of other ingredients, such as, sodium chloride, calcium chloride, glycine and benzethonium chloride to aid somewhat as a preservative when the thrombin is stored in dry or powdered form. It has been applied in the past in solution form directly to cuts or injuries or used in combination with other hemostatic agents, such as an absorbable gelatin sponge which is applied following the closure of a surgical incision and the sponge gradually absorbed over a long period. None, however, has satisfactorily devised a method or formulation of thrombin by which it can be prepackaged, sealed and stored in solution form for subsequent application to a wound. U.S. Pat. No. 2,433,299 to Siegers is directed to the preservation of thrombin by storage in a sucrose solution which together with a saline solution can be sprayed or applied to a bleeding tissue. If anything, however, this patent highlights the problems associated with the preservation of thrombin and the sucrose solution does not make it practically usable as a prepackaged substance for clotting.
A significant difficulty that must be appreciated is the need to provide a product capable of movement in commerce. The product must have an acceptable shelf life under thermal conditions to which a prepackaged plasma clotting composition may expect to be subjected.